determination of the clonality profile in myeloproliferative neoplasms and association with the thrombotic complications (clojak)

Conditions: Myeloproliferative Neoplasm

Summary: myeloproliferative neoplasms (mpn) are associated with an increased risk of thrombosis. platelets, red blood cells (rbc), leukocytes and endothelial cells are involved in these complications. an association with the jak2v617f allele burden assessed in leukocytes has also been suggested. in some patients the allele burden measured in platelets and red blood cells is higher than the one determined in leukocytes. our project aims at associating the risk of thrombosis with the allele burden determined in the cell populations (platelets, red blood cells, granulocytes and endothelial cells) and identifying high-risk clonality profiles.

myeloproliferative neoplasms (mpn) are hematological malignancies associated with an increased risk of thrombosis. although different cell types have been involved in these complications (platelets, red blood cells, leucocytes and endothelial cells), there do not exist any reliable biomarker to predict the thrombotic risk in mpn patients. while some studies suggested that the jak2v617f allele burden measured in leukocytes was associated with the risk of thrombosis, other studies did not confirm these results. besides, a recent work demonstrated that in some patients, the jak2v617f allele burden measured in platelets and red blood cells was higher than the one determined in leukocytes. moreover, some patients present jak2v617f mutated endothelial cells, known as pro-thrombotic in in vitro and animal models. the clojak project will search for an association between the thrombotic risk in mpn and the proportion of cells carrying the jak2v617f mutation in erythroid cells and platelets or its presence in endothelial cells. the objective is to determine a clonality profile (i.e. the profile of repartition of the jak2v617f allele burden in the different hematopoietic and endothelial lineages) associated with the occurrence of thrombosis in mpn patients. one hundred and twenty pv and et patients will be studied at diagnosis. their platelets, red blood cells, granulocytes and endothelial cells will be isolated. the jak2v617f allele burden will be measured in these cells thanks to a digital pcr technic. an association between the clonality profile and the existence of a thrombosis at diagnosis, the mpn phenotype (pv or et), the ipset-thrombosis score and the type of thrombosis (venous, arterial, splanchnic) will be searched.

Eligibility criteria:
inclusion criteria: * adult patient (age ≥ 18 years) * inclusion at diagnosis or during the year following the diagnosis of pv or et (2016 who criteria except bone marrow biopsy that is optional), before introduction of a cytoreductive treatment * patient carrying a jak2v617f mutation * subject registered with a social security scheme * written informed consent obtained * acceptance of inclusion in the fimbank registry (specific consent form needed) exclusion criteria: * et or pv patient not carrying a jak2v617f mutation * patient with cytoreductive treatment (hydroxyurea, anagrelide, interferon, ruxolitinib or other chemotherapy) at the time of blood sampling * person under judicial safeguards, trustee or curatorship * person unable to give her consent * non-cooperative person * exclusion period after another clinical study or participation to another clinical study in the 30 days before inclusion

Keywords: myeloproliferative neoplasms thrombosis clonality jak2v617f